MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

Abstract Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isola...

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Autores principales:	Jih-Yang Ko, Mel S. Lee, Wei-Shiung Lian, Wen-Tsan Weng, Yi-Chih Sun, Yu-Shan Chen, Feng-Sheng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa91fc2b14564efc8f14940ec11fcee4
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spelling	oai:doaj.org-article:fa91fc2b14564efc8f14940ec11fcee42021-12-02T11:40:51ZMicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF10.1038/s41598-017-03616-w2045-2322https://doaj.org/article/fa91fc2b14564efc8f14940ec11fcee42017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03616-whttps://doaj.org/toc/2045-2322Abstract Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.Jih-Yang KoMel S. LeeWei-Shiung LianWen-Tsan WengYi-Chih SunYu-Shan ChenFeng-Sheng WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jih-Yang Ko Mel S. Lee Wei-Shiung Lian Wen-Tsan Weng Yi-Chih Sun Yu-Shan Chen Feng-Sheng Wang MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
description	Abstract Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.
format	article
author	Jih-Yang Ko Mel S. Lee Wei-Shiung Lian Wen-Tsan Weng Yi-Chih Sun Yu-Shan Chen Feng-Sheng Wang
author_facet	Jih-Yang Ko Mel S. Lee Wei-Shiung Lian Wen-Tsan Weng Yi-Chih Sun Yu-Shan Chen Feng-Sheng Wang
author_sort	Jih-Yang Ko
title	MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
title_short	MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
title_full	MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
title_fullStr	MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
title_full_unstemmed	MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
title_sort	microrna-29a counteracts synovitis in knee osteoarthritis pathogenesis by targeting vegf
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fa91fc2b14564efc8f14940ec11fcee4
work_keys_str_mv	AT jihyangko microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT melslee microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT weishiunglian microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT wentsanweng microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT yichihsun microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT yushanchen microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf AT fengshengwang microrna29acounteractssynovitisinkneeosteoarthritispathogenesisbytargetingvegf
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MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF

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